Ferroptosis-centered Drug Response Information

General Information of the Drug (ID: ferrodrug0025)
Name
Glycyrrhizin
Synonyms
Glycyrrhizic acid; glycyrrhizin; 1405-86-3; Glycyrrhizinic acid; Glycyron; Glycyrrhetinic acid glycoside; potenlini; Glizigen; glycyrrhizate; glyzyrrhizin; 18-beta-Glycyrrhizic acid; beta-Glycyrrhizin; 18beta-Glycyrrhizic acid; Glycyrrizin; Rizinsan K2 A2 (free acid); HSDB 496; CHEBI:15939; EINECS 215-785-7; Glycyrrhizin [JAN]; .beta.-glycyrrhizin; NSC 167409; NSC 234419; NSC-167409; NSC-234419; UNII-6FO62043WK; BRN 0077922; CCRIS 8444; DTXSID8047006; 6FO62043WK; C42H62O16; 18.beta.-glycyrrhizic acid; Glycyrrhizinate; CHEMBL441687; NSC 2800; DTXCID6027006; 4-18-00-05156 (Beilstein Handbook Reference); (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl-2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid; 20beta-Carboxy-11-oxo-30-norolean-12-en-3beta-yl-2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid; 30-hydroxy-11,30-dioxoolean-12-en-3beta-yl (2-O-beta-D-glucopyranosyluronic acid)-alpha-D-glucopyranosiduronic acid; alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-; alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl-2-O-beta-D-glucopyranuron osyl-; GLYCYRRHIZIN (II); GLYCYRRHIZIN [II]; Glycyrrhitin; Dermacrin; (3beta,20beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid; GLYCYRRHIZIC ACID (MART.); GLYCYRRHIZIC ACID [MART.]; GLYCYRRHIZIC ACID (USP-RS); GLYCYRRHIZIC ACID [USP-RS]; NSC167409; Glycyram; Neo-Umor; Acid, Glycyrrhizic; (2S,3S,4S,5R,6S)-6-{[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,14,14a,14b-icosahydropicen-3-yl]oxy}-5-{[(2R,3R,4S,5S,6S)-6-carboxy-3,4,5-trihydroxyoxan-2-yl]oxy}-3,4-dihydroxyoxane-2-carboxylic acid; CAS-1405-86-3; Acid, Glycyrrhizinic; MFCD00065194; NSC234419; NCGC00183128-01; (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxy-tetrahydropyran-3-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid; ammonium-glycyrrhizinate; Glycyrrhizic acid, 2K; beta-Glycyrrhizinic acid; GLYCYRRHIZIN [HSDB]; SCHEMBL17684; alpha-D-glucopyranosiduronic acid, (3 beta,20 beta)-20-carboxy-11-oxo-30-norolean-12-en-3-yl 2-O-beta-D-glucopyranuronosyl-; BIDD:ER0363; GLYCYRRHIZIC ACID [MI]; GTPL4688; GLYCYRRHIZIC ACID [INCI]; Glycyrrhizin (Glycyrrhizic Acid); LPLVUJXQOOQHMX-QWBHMCJMSA-N; GLYCYRRHIZIC ACID [WHO-DD]; HY-N0184; Tox21_111520; Tox21_113426; Tox21_303493; BDBM50185127; HMDB:0029843; s2302; AKOS015893086; AKOS015969345; CCG-270511; CS-7695; DB13751; GM-1292; NCGC00257455-01; NCGC00386162-01; NCGC00386162-02; (3beta,20beta)-20-Carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-beta-1- 7-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid; alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-beta-1- 7-glucopyranuronosyl-; AS-13001; E958; G0150; AB01566834_01; EN300-25023649; Q418705; Q-201172; BRD-K83486494-318-01-5; GLYCYRRHIZIC ACID (GLYCYRRHIZIN) (CONSTITUENT OF LICORICE); GLYCYRRHIZIC ACID (GLYCYRRHIZIN) (CONSTITUENT OF LICORICE) [DSC]; Glycyrrhizic acid, United States Pharmacopeia (USP) Reference Standard; Glycyrrhizic Acid, Pharmaceutical Secondary Standard; Certified Reference Material; (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid; (2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylicacid; (3.beta.,20.beta.)-20-Carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-.beta.-1- 7-glucopyranuronosyl-.alpha.-D-glucopyranosiduronic acid; (3.BETA.,20.BETA.)-20-CARBOXY-11-OXO-30-NOROLEAN-12-EN-3-YL 2-O-.BETA.-D-GLUCOPYRANURONOSYL-.ALPHA.-D-GLUCOPYRANOSIDURONIC ACID; (3beta,20beta)-20-Carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-beta-1-7-glucopyranuronosyl-alpha-D-glucopyranosiduronic acid; 20BETA-CARBOXY-11-OXO-30-NOROLEAN-12-EN-3BETA-YL-2-O-BE TA-D-GLUCOPYRANURONOSYL-ALPHA-D-GLUCOPYRANOSIDURONIC ACID; alpha-D-Glucopyranosiduronic acid, (3beta,20beta)-20-carboxy-11-oxo-30-norlean-12-en-3-yl-2-O-beta-1-7-glucopyranuronosyl-

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Status
Phase 3
Drug Type
Small molecular drug
Structure
3D MOL
2D MOL
Formula
C42H62O16
IUPAC Name
(2S,3S,4S,5R,6R)-6-[(2S,3R,4S,5S,6S)-2-[[(3S,4aR,6aR,6bS,8aS,11S,12aR,14aR,14bS)-11-carboxy-4,4,6a,6b,8a,11,14b-heptamethyl-14-oxo-2,3,4a,5,6,7,8,9,10,12,12a,14a-dodecahydro-1H-picen-3-yl]oxy]-6-carboxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid
Canonical SMILES
CC1(C2CCC3(C(C2(CCC1OC4C(C(C(C(O4)C(=O)O)O)O)OC5C(C(C(C(O5)C(=O)O)O)O)O)C)C(=O)C=C6C3(CCC7(C6CC(CC7)(C)C(=O)O)C)C)C)C
InChI
InChI=1S/C42H62O16/c1-37(2)21-8-11-42(7)31(20(43)16-18-19-17-39(4,36(53)54)13-12-38(19,3)14-15-41(18,42)6)40(21,5)10-9-22(37)55-35-30(26(47)25(46)29(57-35)33(51)52)58-34-27(48)23(44)24(45)28(56-34)32(49)50/h16,19,21-31,34-35,44-48H,8-15,17H2,1-7H3,(H,49,50)(H,51,52)(H,53,54)/t19-,21-,22-,23-,24-,25-,26-,27+,28-,29-,30+,31+,34-,35-,38+,39-,40-,41+,42+/m0/s1
InChIKey
LPLVUJXQOOQHMX-QWBHMCJMSA-N
PubChem CID
14982
TTD Drug ID
D0T8QB
Full List of Ferroptosis Target Related to This Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [1]
Target for Ferroptosis Suppressor
Responsed Disease Hypoxic ischemic brain injury ICD-11: 8B24
 Disease Info 
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Fatty acid metabolism hsa01212
Cell Process Cell ferroptosis
In Vitro Model rPCNs (Rat primary cortical neurons)
In Vivo Model
Male and female neonatal SpragueDawley rats on postpartum day 7 (P7) were provided by SPF Biotechnology (Beijing, China). Each animal was anesthetized with isoflurane (4% for induction, 2% for maintenance), the skin was incised, and the left common carotid artery was exposed. This artery was ligated with a 5-0 suture and cut, and the skin was sutured closed. Next, the pups recovered for 1 h with their mother. Subsequently, the pups were placed in a hypoxia chamber (8% O2 + 92% N2 mixture) for 2 h. After 2 h of hypoxia, the animals were placed back with their dam.

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Response regulation Glycyrrhizin (GL) not only inhibited ferroptosis induced by RSL3 and oxygen-glucose deprivation in vitro but also inhibited ferroptosis induced by hypoxic-ischemic brain damage (HIBD) in vivo. GL could suppress the occurrence of neuronal ferroptosis and reduce neuronal loss in HIBD via the HMGB1/GPX4 pathway.
Unspecific Target
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Responsed Disease Hepatoblastoma ICD-11: DB91
 Disease Info 
Responsed Regulator High mobility group protein B1 (HMGB1) Driver
 Regulator Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.

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Response regulation The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased.
Nuclear factor erythroid 2-related factor 2 (NFE2L2)
 Target Info 
In total 1 item(s) under this Target
Experiment 1 Reporting the Ferroptosis-centered Drug Act on This Target [2]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Hepatoblastoma ICD-11: DB91
 Disease Info 
Pathway Response Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model L-02 cells Endocervical adenocarcinoma Homo sapiens CVCL_6926
In Vivo Model
In total, 40 male specific- pathogen-free C57BL/6 mice (Hubei Animal Experimental Center) 6-8 weeks old. The mice were randomly divided into 5 groups: The normal group, model group, 15 mg/kg GLY group, 30 mg/kg GLY group and 60 mg/kg GLY group. Except for the normal group, the other four groups of mice were injected intraperitoneally with D-GalN (400 mg/kg) and LPS (100 ug/kg) to induce the ALF model. According to a previous study on GLY gavage doses, three doses of GLY (15, 30 and 60 mg/kg/day) intervention groups were used. A total of 24 mice were divided into three groups. Mice received gavage with different doses of GLY for 3 days before induction of the ALF model.

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Response regulation The HMGB1 inhibitor glycyrrhizin (GLY) significantly reduced the degree of ferroptosis during acute liver failure (ALF) by inhibiting oxidative stress. Treatment with GLY reduced the degree of liver damage, the expression of HMGB1 was decreased, and the levels of Nrf2, HO1 and GPX4 were increased.
References
Ref 1 Glycyrrhizin Attenuates Hypoxic-Ischemic Brain Damage by Inhibiting Ferroptosis and Neuroinflammation in Neonatal Rats via the HMGB1/GPX4 Pathway. Oxid Med Cell Longev. 2022 Apr 7;2022:8438528. doi: 10.1155/2022/8438528. eCollection 2022.
Ref 2 Mechanism of glycyrrhizin on ferroptosis during acute liver failure by inhibiting oxidative stress. Mol Med Rep. 2019 Nov;20(5):4081-4090. doi: 10.3892/mmr.2019.10660. Epub 2019 Sep 10.